The present invention provides a method of producing human immortalized megakaryocytes and / or human immortalized
megakaryocyte progenitors and / or a human
megakaryocytic cell line (102) from adult CD34+ HSPCs (100) capable of maturing towards functional megakaryocytes (103) that produce functional platelets (104), the method at least comprising a step of enforcing expression of at least one
gene by introducing an
expression cassette comprising at least one
gene into the CD34+ HSPCs (100) by transduction, in particular lentiviral (LV) transduction, wherein the transduced CD34+ HSPCs (100) are configured to express at least one
gene from the HOXL subclass of ANTP
homeobox class family and / or the TALE
homeobox class family upon induction of expression by an activator, and constitutively express at least one antiapoptotic gene from the BCL2 family, wherein the transduced CD34+ HSPCs (100) are immortalized through expression of the at least one gene from the HOXL subclass of the ANTP
homeobox class family and / or the TALE homeobox class family, preferably wherein the at least one gene from the HOXL subclass includes one among HOXB8, HOXA7, HOXA10, or HOXB4 gene in combination with at least one among MEIS1, MEIS2, MEIS3, PBX1, PBX2, PBX3, and / or PBX4 gene, while the at least one antiapoptotic gene from the BCL2 family includes BCL2L1 or BCL2L2. The invention further provides a method of producing a functional
platelet by using immortalized megakaryocytes and / or immortalized
megakaryocyte progenitors and / or an immortalized
megakaryocytic cell line obtained through the above-described method. Still further, the invention provides a pharmaceutical composition comprising functional platelets obtained through the above-described method, and therapeutic uses thereof.